RESUMO
The main objective of the current research was to develop a compendial flow-through cell apparatus based in vitro release testing method for sustained-release triamcinolone acetonide-loaded poly (lactic-co-glycolic) acid (PLGA) microspheres. Media-based and instrument-based parameters, such as surfactant type, concentration, media volume, flow rate, and testing temperature, were investigated. In addition, a detailed exploration was performed to reveal polymer degradation encompassing pore formation, channeling, and triamcinolone acetonide release from microspheres using freeze-fracture scanning electron microscopy. The developed USP apparatus 4 method demonstrated more than 85% drug release from the microspheres in 12 days and showcased reproducibility between different microsphere batches. Large medium volume (15 times saturation solubility) at low surfactant concentration was identified as a critical media-based parameter, with potential application in testing of other sensitive poorly soluble drugs. At 35 °C, drug release via pore channeling to the surface was evident, whereas at 39 °C, drug release slowed due to polymer plasticization. It was demonstrated here for the first time that elevated temperature-accelerated testing does not work for all PLGA-based microsphere products.
Assuntos
Portadores de Fármacos/química , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Triancinolona Acetonida/farmacocinética , Química Farmacêutica/métodos , Microscopia Crioeletrônica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Reprodutibilidade dos Testes , Solubilidade , Temperatura , Triancinolona Acetonida/administração & dosagemRESUMO
This review article is focused on the sterilization techniques used for polymer-based implantable medical devices as well as the regulatory aspects governing sterile medical devices. Polymeric materials are increasingly used in implantable devices due to their biodegradable and biocompatible nature. Patients and medical staff often prefer long-term implantable devices and these can be achieved using high molecular weight polymers. Sterilization of polymer-based implantable devices is critical. Since all implantable devices must be sterile, the effect of the sterilization method on the different device components (such as, the polymer, the drug, the electronics, etc.) has to be considered. A comprehensive summary of the established sterilization methods is provided along with the possible effects on polymers. In addition, novel sterilization methods are also discussed.
